Background: A consensus conference on multiple system atrophy (MSA) in 1998 established criteria for diagnosis that have been accepted widely. Since then, clinical, laboratory, neuropathologic, and imaging studies have advanced the field, requiring a fresh evaluation of diagnostic criteria. We held a second consensus conference in 2007 and present the results here. Methods: Experts in the clinical, neuropathologic, and imaging aspects of MSA were invited to participate in a 2-day consensus conference. Participants were divided into five groups, consisting of specialists in the parkinsonian, cerebellar, autonomic, neuropathologic, and imaging aspects of the disorder. Each group independently wrote diagnostic criteria for its area of expertise in advance of the meeting. These criteria were discussed and reconciled during the meeting using consensus methodology. Results: The new criteria retain the diagnostic categories of MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia to designate the predominant motor features and also retain the designations of definite, probable, and possible MSA. Definite MSA requires neuropathologic demonstration of CNS α-synuclein–positive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Probable MSA requires a sporadic, progressive adult-onset disorder including rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult-onset disease including parkinsonism or cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus one other feature that may be a clinical or a neuroimaging abnormality. Conclusions: These new criteria have simplified the previous criteria, have incorporated current knowledge, and are expected to enhance future assessments of the disease.

There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2–receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group, 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (±SD) daily doses given by the end of the study were 16.5±6.6 mg of ropinirole (plus 427±221 mg of levodopa in patients who received supplementation) and 753±398 mg of levodopa (including supplements). Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.